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Pathogenesis of Lassa fever in cynomolgus macaques.

Hensley LE, Smith MA, Geisbert JB, Fritz EA, Daddario-DiCaprio KM, Larsen T, Geisbert TW - Virol. J. (2011)

Bottom Line: Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

ABSTRACT

Background: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

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Related in: MedlinePlus

Histopathology and immunohistochemistry liver and adrenal gland of Lassa virus-infected cynomolgus monkeys. Histology of liver showing inflammation at days 7 (A) and 15 (B); H&E stain. Note the progression of increased immunostaining (brown) of hepatocytes (C) and adrenal cortical cells (E) from day 7 to day 15 (D, liver; F, adrenal gland). Original magnifications, ×10 (A, B, D, F), ×20 (C, E).
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Figure 8: Histopathology and immunohistochemistry liver and adrenal gland of Lassa virus-infected cynomolgus monkeys. Histology of liver showing inflammation at days 7 (A) and 15 (B); H&E stain. Note the progression of increased immunostaining (brown) of hepatocytes (C) and adrenal cortical cells (E) from day 7 to day 15 (D, liver; F, adrenal gland). Original magnifications, ×10 (A, B, D, F), ×20 (C, E).

Mentions: Histologically, the severity of hepatic changes varied between animals at day 7. The most noteworthy lesions were lymphoplasmacytic and neutrophilic inflammation (2/3) (Figure 8A). LASV antigen was detected in Kupffer cells and hepatocytes (3/3) at day 7 (Figure 8C). Lymphoplasmacytic and neutrophilic inflammation was more pronounced in the terminal animals (3/3) (Figure 8B). LASV immunostaining increased substantially at terminal time points (Figure 8D) with increased numbers of immunopositive hepatocytes (3/3). PTAH staining demonstrated multifocal distribution of small fibrin deposits in sinusoids (Figure 7B) and vessels (Figure 7C).


Pathogenesis of Lassa fever in cynomolgus macaques.

Hensley LE, Smith MA, Geisbert JB, Fritz EA, Daddario-DiCaprio KM, Larsen T, Geisbert TW - Virol. J. (2011)

Histopathology and immunohistochemistry liver and adrenal gland of Lassa virus-infected cynomolgus monkeys. Histology of liver showing inflammation at days 7 (A) and 15 (B); H&E stain. Note the progression of increased immunostaining (brown) of hepatocytes (C) and adrenal cortical cells (E) from day 7 to day 15 (D, liver; F, adrenal gland). Original magnifications, ×10 (A, B, D, F), ×20 (C, E).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104370&req=5

Figure 8: Histopathology and immunohistochemistry liver and adrenal gland of Lassa virus-infected cynomolgus monkeys. Histology of liver showing inflammation at days 7 (A) and 15 (B); H&E stain. Note the progression of increased immunostaining (brown) of hepatocytes (C) and adrenal cortical cells (E) from day 7 to day 15 (D, liver; F, adrenal gland). Original magnifications, ×10 (A, B, D, F), ×20 (C, E).
Mentions: Histologically, the severity of hepatic changes varied between animals at day 7. The most noteworthy lesions were lymphoplasmacytic and neutrophilic inflammation (2/3) (Figure 8A). LASV antigen was detected in Kupffer cells and hepatocytes (3/3) at day 7 (Figure 8C). Lymphoplasmacytic and neutrophilic inflammation was more pronounced in the terminal animals (3/3) (Figure 8B). LASV immunostaining increased substantially at terminal time points (Figure 8D) with increased numbers of immunopositive hepatocytes (3/3). PTAH staining demonstrated multifocal distribution of small fibrin deposits in sinusoids (Figure 7B) and vessels (Figure 7C).

Bottom Line: Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

ABSTRACT

Background: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

Show MeSH
Related in: MedlinePlus